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Abstract

The development of voltage-sensitive dyes has revolutionized cardiac electrophysiology and made optical imaging of cardiac electrical activity possible. Photon diffusion models coupled to electrical excitation models have been successful in qualitatively predicting the shape of the optical action potential and its dependence on subsurface electrical wave orientation. However, the accuracy of the diffusion equation in the visible range, especially for thin tissue preparations, remains unclear. Here, we compare diffusion and Monte Carlo (MC) based models and we investigate the role of tissue thickness. All computational results are compared to experimental data obtained from intact guinea pig hearts. We show that the subsurface volume contributing to the epi-fluorescence signal extends deeper in the tissue when using MC models, resulting in longer optical upstroke durations which are in better agreement with experiments. The optical upstroke morphology, however, strongly correlates to the subsurface propagation direction independent of the model and is consistent with our experimental observations.

Figures (9)

A schematic representation of a typical cardiac epi-fluorescence experiment in isolated guinea pig hearts. In this setup the epicardial surface of the heart is uniformly illuminated by a light source (e.g. a tungsten-halogen lamp), whose light has been bandpass filtered at the appropriate wavelengths for excitation of the VSD. Fluorescence optical signals of cardiac electrical activity are then recorded using a CCD camera from the same epicardial area at the appropriate wavelength. A typical optical action potential as recorded from a single image pixel is shown on the right.

Subsurface wave front orientation and VF*. The green area caricaturizes the subsurface volume from which contributions are made to the optical signal in the pixel of interest (dashed arrows). Panel A shows isochrones (white lines).of a wave front propagating towards the epicardium, whereas Panel B shows the opposite situation. The optical signal recorded from the pixel of interest on the epicardial surface is shown on top, as well as VF* (black circle).

Excitation fluence and intramural optical weight. Panels A and B show the intramural excitation fluence Φe for two different tissue thicknesses (2.5 and 5mm respectively). The data was normalized to the photon density on the epicardial surface (z=0). Panel C and D show the relative contribution of an intramural layer at depth z to the total fluorescence for a uniform source distribution for two different tissue thicknesses (2.5 and 5mm respectively).

Optical activation maps and optical upstrokes. The three left panels show simulated activation maps obtained using the different photon transport models. An experimental activation map is shown on the right, as well as a comparison of optical upstrokes obtained from the pixel indicated by an asterisk * in the activation maps.

Differences in optical upstroke durations in the various models. The left panels show color-coded maps of the differences in optical upstroke durations in each pixel between the diffusion models and the MC model. The tracings on the right compare the optical upstrokes of the three models recorded from two different areas (a and b).

Linear regression analysis of VF* vs ϕF for the different photon transport models. Each dot in the scatter plot indicates the results obtained for a single pixel and the red line shows the linear fit to the data.

Reconstructing subsurface wave front orientation from VF* maps for epicardial pacing (top) and sinus rhythm (bottom). For each row, the VF* map is shown on the left and the reconstructions using the different models are shown on the right.